PhD position 8: Endothelial-derived inhibiting and activating pathways of platelets in thrombosis (Dortmund/Maastricht/Mainz)

We offer a PhD position for biomedical doctoral students at the Leibniz-Institut für Analytische Wissenschaften, ISAS (Dortmund, Germany), the School for Cardiovascular Disease in Maastricht (CARIM, Netherlands) and the Center for Thrombosis and Hemostasis (Mainz, Germany). As this project is part of the MSCA ITN “Thrombo-Inflammation in Cardiovascular Disease” (TICARDIO), you will be trained in an international, interdisciplinary joint doctoral degree program striving to train the next generation of biomedical researchers. Your PhD project will be supervised by Prof. Dr. Albert Sickmann in Dortmund and Prof. Dr. Johan Heemskerk in Maastricht and PD Dr. Kerstin Jurk in Mainz.

Activities and responsibilities

Project description
In healthy vessels, the endothelium produces the vasoactive mediators NO and prostacyclin, which relax blood vessels and inhibit platelet activation by acting through PKA and PKG signaling. Based on pilot phospho-proteome data, it is hypothesized that major targets of PKA and PKG signaling are the platelet complex LRMP located in the ER along with the non-receptor cytoplasmic tyrosine kinase Syk mediated GPIbα- and GPVI-signaling, thereby modulating key platelet activation processes implicated in thrombosis and inflammation.
The project first aims to unravel phospho-proteomic signatures of LRMP and GPIbα-/GPVI-Syk signalosomes reflecting impaired endothelial cell functions and revealing potential biomarkers. You will perform the quantitative assessment of inhibitory pathways in platelets derived from thrombo-inflammation subjects by parallel reaction monitoring (PRM). The second aim is to pursue the mechanistic elucidation of the inhibitory signaling pathways that regulate platelet functions. In order to investigate the impact of endothelial-derived prostacyclin and NO on platelet functions (aggregometry, flow cytometry, platelet-based thrombin generation) and platelet signaling a comprehensive comparative study with healthy versus well characterized thrombo-inflammation disorders has to be conducted. The third aim is to verify biochip models of thrombo-inflammation assessing the anti-platelet activities of the endothelium. Pathways in multi-parameter thrombus formation using vascular chip models will be analyzed. Finally, the fourth aim is to link the LRMP activity to phosphorylation changes in the GPIbα-/GPVI-Syk signalosome, which control platelet adhesion to the extracellular matrix.

Qualification profile

>> You have a Master degree (or equivalent) in biomedical sciences or a similar field
>> You are in the first four years of your research career and do not hold a doctoral degree
>> Your must not have resided in Germany for more than 12 months in the 3 years prior to the recruitment
>> Ideally, you have experience in cell culture and functional studies, mass spectrometry based proteomics and analytical and bioinformatical skills

Benefits

Benefits of working in an ITN
>> You will be working within our international group of > 30 researchers
>> You will be involved in cutting-edge research in an interdisciplinary environment
>> You will contuct your research at three academic and non-academic research locations
>> You will receive excellent network-wide and local training with conference participation
>> You will receive a 36 months contract with all national social security (and family allowance, if applicable) at ISAS.
>> You will optain a joint doctoral degree from Universities of Maastricht and Mainz, if all requirements are fullfilled

How to apply
Please visit www.ticardio.eu for information about the recruitment process and all required application documents.

Application deadline: July 15, 2019

Send application to

How to apply
Please visit www.ticardio.eu for information about the recruitment process and all required application documents.

While applying for the job please refer to jobvector and use the following reference number: JV-50056785

About Universitätsmedizin Mainz

Center for thrombosis and hemostasis The scientific activities of the researching physicians and scientists of the medical units of the Mainz University Medical Center are characterized by a broad content spectrum. In recent years, university medicine has been able to confirm its national and international position through a large number of excellent publications and the acquisition of...
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